The glucose infusion rate of parenteral nutrition in the first week of life in preterm infants: an observational study

Background Most preterm infants require a continuous glucose infusion in the early postnatal period due to the interruption of the transplacental glucose supply after birth to promote better neurodevelopmental outcomes. Aims To investigate the glucose infusion rate (GIR) on parenteral nutrition (PN) in the first week of life administered in preterm infants and its effect on neonatal morbidity and mortality. Methods This study included 97 infants aged < 37 gestational weeks and weighed < 2500 g at birth. Infants recruited in this study were classified into 3 groups based on the GIR usage in parenteral nutrition as follows: GIR usage of 5- < 7 g/kg/day (Group I), GIR usage of 7–13 g/kg/day (Group II), and GIR usage of > 13–15 g/kg/day (Group III). Univariate and multivariate logistic regression analyzes were carried out to investigate whether the GIR usage in the three groups was associated with selected neonatal morbidities and mortality. Neonatal morbidities analyzed included respiratory distress syndrome (RDS), necrotizing enterocolitis, sepsis, retinopathy of prematurity, pulmonary hypertension, hypoglycemia, and hyperglycemia. Result Of 97 preterm infants included, 51.5% infants had a gestational age of 34- < 37 weeks, and 54.6% infants had a birth weight of 1500- < 2500 g. The multivariate logistic regression analysis showed that the GIR usage of 5- < 7 g/kg/day was an independent variable that significantly increased the risk of hypoglycemia (Adjusted Odds Ratio [AOR] = 4.000, 95% Confidence Interval [CI] = 1.384–11.565, P = 0.010) and reduced the risk of sepsis (AOR = 0.096, 95% CI = 0.012–0.757, P = 0.026). The GIR usage in all three groups did not increase the risk of mortality. For neonatal morbidity analyzed in this study, RDS (AOR = 5.404, 95%CI = 1.421–20.548, P = 0.013) was an independent risk factor of mortality. Conclusion The GIR usage of < 7 g/kg/day in PN in the first week of life administered to preterm infants was an independent variable in increasing hypoglycemia, but in contrast, reducing the risk of sepsis.

Insulin regulates GLUT4 in the ventromedial hypothalamus to restore the sympathoadrenal response to hypoglycemia in diabetic rats

It is proposed that the impaired counterregulatory response (CRR) to hypoglycemia in insulin-deficient diabetes may be due to chronic brain insulin deficiency. To test this hypothesis, streptozotocin-induced diabetic Sprague-Dawley rats were infused with insulin (3 mU/day) or artificial cerebrospinal fluid (aCSF) bilaterally into the ventromedial hypothalamus (VMH) for 2 wk and compared with nondiabetic rats. Rats underwent hyperinsulinemic (50 mU·kg−1·min−1)-hypoglycemic (~45 mg/dl) clamps. Diabetic rats demonstrated an impaired CRR to hypoglycemia, noted by a high glucose infusion rate and blunted epinephrine and glucagon responses. The defective sympathoadrenal response was restored by chronic infusion of insulin into the VMH. Diabetic rats had decreased VMH Akt phosphorylation and decreased VMH glucose transporter 4 (GLUT4) content, which was also restored by chronic infusion of insulin into the VMH. Separate experiments in nondiabetic rats in which GLUT4 translocation into the VMH was inhibited with an infusion of indinavir were notable for an impaired CRR to hypoglycemia, indicated by increased glucose infusion rate and diminished epinephrine and glucagon responses. Results suggest that, in this model of diabetes, VMH insulin deficiency impairs the sympathoadrenal response to hypoglycemia and that chronic infusion of insulin into the VMH is sufficient to normalize the sympathoadrenal response to hypoglycemia via restoration of GLUT4 expression in the VMH.

Phenotypic Characterization of Insulin-Resistant and Insulin-Sensitive Obesity

Context: Whereas insulin resistance and obesity coexist, some obese individuals remain insulin sensitive. Objective: We examined phenotypic and metabolic factors associated with insulin sensitivity in both muscle and liver in obese individuals. Design and Participants: Sixty-four nondiabetic obese adults (29 males) underwent hyperinsulinemic (15 and 80 mU/m2 · min)-euglycemic clamps with deuterated glucose. Top tertile subjects for glucose infusion rate during the high-dose insulin clamp were assigned Musclesen and those in the lower two tertiles were assigned Muscleres. Secondarily, top tertile subjects for endogenous glucose production suppression during the low-dose insulin clamp were deemed Liversen and the remainder Liverres. Main Outcomes Measures: Clinical and laboratory parameters and visceral, subcutaneous, liver, and pancreatic fat were compared. Results: Musclesen and Muscleres had similar body mass index and total fat (P &gt; .16), but Musclesen had lower glycated hemoglobin (P &lt; .001) and systolic (P = .01) and diastolic (P = .03) blood pressure (BP). Despite similar sc fat (P = 1), Musclesen had lower visceral (P &lt; .001) and liver (P &lt; .001) fat. Liversen had lower visceral (P &lt; .01) and liver (P &lt; .01) fat and C-reactive protein (P = .02) than Liverres. When subjects were grouped by both glucose infusion rate during the high-dose insulin clamp and endogenous glucose production suppression, insulin sensitivity at either muscle or liver conferred apparent protection from the adverse metabolic features that characterized subjects insulin resistant at both sites. High-density lipoprotein-cholesterol, 1-hour glucose, systolic BP, and triglycerides explained 54% of the variance in muscle insulin sensitivity. Conclusions: Obese subjects who were insulin sensitive at muscle and/or liver exhibited favorable metabolic features, including lower BP, liver and visceral adiposity. This study identifies factors associated with, and possibly contributing to, insulin sensitivity in obesity.

Acute exercise increases insulin sensitivity in adult sheep: a new preclinical model

In healthy humans and rodents, chronic and acute exercise improves subsequent insulin sensitivity of skeletal muscle. A large animal species with similar metabolic responses to exercise would permit longitudinal studies, including repeated biopsies of muscle and other tissues not possible in rodents, and enable study of interactions with insulin-resistant physiological states not feasible in humans. Therefore, we examined whether acute exercise increases insulin sensitivity in adult sheep. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp (HEC) in mature female sheep ( n = 7). Sheep were familiarized to treadmill walking and then performed an acute exercise bout (30 min, 8% slope, up to 4.4 km/h). A second HEC was conducted ∼18 h after the acute exercise. Musculus semimembranosus biopsies were obtained before and after each HEC. Glucose infusion rate during the HEC increased 40% ( P = 0.003) and insulin sensitivity (glucose infusion rate/plasma insulin concentration) increased 32% ( P = 0.028) after acute exercise. Activation of proximal insulin signaling in skeletal muscle after the HEC, measured as Ser473 phosphorylation of Akt, increased approximately five-fold in response to insulin ( P < 0.001) and was unaltered by acute exercise performed 18 h earlier. PGC1α and GLUT4 protein, glycogen content and citrate synthase activity in skeletal muscle did not change in response to insulin or exercise. In conclusion, improved insulin sensitivity and unchanged proximal insulin signaling on the day after acute exercise in sheep are consistent with responses in humans and rodents, suggesting that the sheep is an appropriate large-animal model in which to study responses to exercise.